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Farci D, Graça AT, Hall M, Haniewicz P, Kereïche S, Faull P, Kirkpatrick J, Tramontano E, Schröder WP, Piano D
J Struct Biol 217 (1) 108162 [2024-12-13; online 2024-12-13]
Oligomers of the SARS-CoV-2 nucleocapsid (N) protein are characterized by pronounced instability resulting in fast degradation. This property likely relates to two contrasting behaviors of the N protein: genome stabilization through a compact nucleocapsid during cell evasion and genome release by nucleocapsid disassembling during infection. In vivo, the N protein forms rounded complexes of high molecular mass from its interaction with the viral genome. To study the N protein and understand its instability, we analyzed degradation profiles under different conditions by size-exclusion chromatography and characterized samples by mass spectrometry and cryo-electron microscopy. We identified self-cleavage properties of the N protein based on specific Proprotein convertases activities, with Cl- playing a key role in modulating stability and degradation. These findings allowed isolation of a stable oligomeric complex of N, for which we report the 3D structure at ∼6.8 Å resolution. Findings are discussed considering available knowledge about the coronaviruses' infection cycle.
PubMed 39675446
DOI 10.1016/j.jsb.2024.108162
Crossref 10.1016/j.jsb.2024.108162
pii: S1047-8477(24)00102-3